Genetic disorders of human neurological and immune function

人类神经和免疫功能的遗传性疾病

• 批准号: MC_UU_00035/11
• 负责人: Yanick Crow
• 金额: $ 581.93万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00035%2F11
• 关键词: Genetic; disorders; human; neurological; immune

The Crow laboratory has two main interests. Firstly, we study a chemical called interferon, which acts as a kind of cellular disinfectant that kills viruses. Like a disinfectant, too much interferon is dangerous. Interferon is normally only produced when cells sense the presence of viral genetic material (DNA and RNA). However, we have identified patients in whom interferon is high in the absence of viral infection, due to the cell misinterpreting our own DNA and RNA as coming from a virus, and the subsequent triggering of interferon production. We are interested in how cells normally avoid such sensing of ‘self’ as ‘non-self’, and what happens when these mechanisms fail. In a second research theme, we study a rare disease of the blood vessels of the brain called Labrune syndrome, which we discovered to arise due to changes in a piece of genetic material called SNORD118. We have developed a zebrafish which does not have SNORD118. Using this model, we want to understand how the blood vessels in our brain are kept healthy, and how problems with the function of SNORD118 cause disease. This could be relevant not only for the development of future treatments for Labrune syndrome, but also in our understanding of more common disorders of the brain blood vessels, such as stroke.We work closely with affected families, using samples that are provided by patients for our research, together with specialised tests and animal models, to better understand and treat the devastating diseases described above.

Crow实验室有两个主要兴趣。首先，我们研究一种叫做干扰素的化学物质，它可以作为一种细胞消毒剂杀死病毒。就像消毒剂一样，过多的干扰素是危险的。干扰素通常仅在细胞感觉到病毒遗传物质（DNA和RNA）存在时产生。然而，我们已经确定了在没有病毒感染的情况下干扰素高的患者，这是由于细胞将我们自己的DNA和RNA误解为来自病毒，并随后触发干扰素的产生。我们感兴趣的是，细胞通常如何避免将“自我”感知为“非自我”，以及当这些机制失败时会发生什么。在第二个研究主题中，我们研究了一种罕见的大脑血管疾病，称为Labrune综合征，我们发现这种疾病是由于一种名为SNORD 118的遗传物质发生变化而引起的。我们已经开发了一种没有SNORD118的斑马鱼。使用这个模型，我们想了解我们大脑中的血管是如何保持健康的，以及SNORD118功能的问题是如何导致疾病的。这不仅对未来开发Labrune综合征的治疗方法有重要意义，也有助于我们了解更常见的脑血管疾病，如中风。我们与受影响的家庭密切合作，使用患者提供的样本进行研究，结合专门的测试和动物模型，以更好地了解和治疗上述破坏性疾病。

项目成果

Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease

• DOI: 10.1007/s10875-024-01660-6
• 发表时间: 2024-02
• 期刊: Journal of Clinical Immunology
• 影响因子: 9.1
• 作者: Clémence David;Mihaly Badonyi;Robin Kechiche;Antonella Insalaco;M. Zecca;Fabrizio de Benedetti